Benzyloxypyrrolidine derivatives, above all, optically active benzyloxypyrrolidine derivatives are useful compounds as various medicine intermediates, and many processes for production thereof have been known. In particular, when used as a starting material for a medical product, it is essential to procure a high-purity substance.
First, a process for production of a benzyloxypyrrolidine derivative will be described. It is a general method that a nitrogen-containing cyclic alcohol derivative is reacted with benzyl halide in a basic condition. As specific examples, a reaction of 1-tert-butoxycarbonyl-3-hydroxypyrrolidine with benzyl halide is mentioned. In this reaction, halogenation is carried out with benzyl bromide in the presence of sodium hydride (Patent document 1, Non-patent document 1), but it can be said that implementation in an industrial scale is difficult because of using combustible substances such as sodium hydride. Further, as a method for production of a benzyloxypyrrolidine derivative by benzylation of a piperinol derivative, a reaction example in the presence of tetrabutylammonium iodide catalyst is reported (Patent document 2), there is used a benzyl chloride of 11.5 times by mole under solvent-free condition and implementation in an industrial scale is economically difficult.
Further, as a process for production of a hydrochloride of an optically active benzyloxypyrrolidine derivative, there is a report that 3 times by mole of 4 M hydrogen chloride-dioxane solution was added to an optically active benzyloxypyrrolidine derivative, and after 2 hours, toluene was added to a concentrated residue to try crystallization (Patent document 3). However, the hydrochloride of an optically active 3-benzyloxypyrroline derivative obtained by this method is described as syrup. As disclosed above, it is difficult to isolate hydrochloride of an optically active 3-benzyloxypyrroline derivative as powder due to very high hygroscopic property.
As described above, there has been found no example of reports on industrial processes of production of a benzyloxypyrrolidine derivative and hydrochloride powder of an optically active benzyloxypyrrolidine derivative, and further, there has been found no example of reports on a hydrochloride powder of an optically active benzyloxypyrrolidine derivative.    Patent document 1: U.S. Pat. No. 5,854,268 Specification (Example 1)    Patent document 2: International Publication 2004-99137 pamphlet (page 142, 2R in EXAMPLE 1)    Patent document 3: U.S. Pat. No. 5,037,841 Specification (Example 49)    Non-patent document 1: Journal of Medicinal Chemistry (42, 4, 685, 1999)